RRC ID 46254
著者 Xie C, Miyasaka T, Yoshimura S, Hatsuta H, Yoshina S, Kage-Nakadai E, Mitani S, Murayama S, Ihara Y.
タイトル The homologous carboxyl-terminal domains of microtubule-associated protein 2 and TAU induce neuronal dysfunction and have differential fates in the evolution of neurofibrillary tangles.
ジャーナル PLoS One
Abstract Microtubule-associated protein 2 (MAP2) and Tau are abundant neuronal microtubule-associated proteins. Both proteins have highly homologous carboxyl-terminal sequences that function as microtubule-binding domains. Whereas Tau is widely accepted as a pathoetiological factor in human tauopathies, including Alzheimer's disease (AD), it is not known whether there is a relationship between MAP2 and tauopathy. To better understand the pathological roles of MAP2 and Tau, we compared their behaviors in transgenic Caenorhabditis elegans in which MAP2 or Tau was expressed pan-neuronally. Both MAP2 and Tau elicited severe neuronal dysfunction and neuritic abnormalities, despite the absence of detergent-insoluble aggregates in worm neurons. Biochemical analysis revealed that the expressed MAP2 or Tau in worms was highly phosphorylated and did not bind to microtubules. Newly raised antibodies to MAP2 that effectively distinguished between the highly homologous carboxyl-terminal sequences of MAP2 and Tau showed that MAP2 was not involved in the growth process of neurofibrillary tangles in the AD brain. These results indicate that Tau and MAP2 have different fates in the inclusion formation and raise the possibility that MAP2 plays a significant role in neurotoxicity in the AD brain despite the absence of MAP2-aggregates.
巻・号 9(2)
ページ e89796
公開日 2014-1-1
DOI 10.1371/journal.pone.0089796
PII PONE-D-13-30767
PMID 24587039
PMC PMC3934940
MeSH Analysis of Variance Animals Blotting, Western Caenorhabditis elegans / metabolism* Fluorescent Antibody Technique Humans Microtubule-Associated Proteins / genetics* Microtubule-Associated Proteins / metabolism Neurofibrillary Tangles / metabolism* Phosphorylation Protein Structure, Tertiary / genetics Tauopathies / metabolism* tau Proteins / genetics* tau Proteins / metabolism
IF 2.74
引用数 10
WOS 分野 NEUROSCIENCES
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